Liver Injury due to Intravenous Methylprednisolone in the Drug-Induced Liver Injury Network

Liver Int. 2025 Feb;45(2):e16242. doi: 10.1111/liv.16242.

Abstract

Background and aims: Short courses of intravenous (iv) methylprednisolone (MP) can cause drug induced liver injury (DILI). The aim of this study was to assess the clinical features and HLA associations of MP-related DILI enrolled in the US DILI Network (DILIN).

Methods: DILIN cases with MP as a suspected drug were reviewed. DILIN causality scoring was assigned on a 5-point scale (definite, highly likely, probable, possible, unlikely). All cases with MP causality scores of definite, highly likely or probable were analysed. HLA data from direct sequencing were analysed.

Results: Eleven cases of definite, highly likely, or probable MP DILI were identified. The median age was 48 years; 73% were female; median latency to onset was 30 days; 55% were jaundiced; and all had hepatocellular injury with one patient requiring transplantation. Nine of the 11 cases were in patients with multiple sclerosis (MS). Liver biopsies in 7 cases revealed mild acute hepatitis with/without cholestasis. HLA data demonstrated that HLA-DRB1*15:01, the primary HLA class II allele associated with MS was over-represented. HLA-DQB1*06:02-HLA-DQA1*01:02 which is haplotypic with the HLA-DRB1*15 haplotype was more common in the MP DILI cases compared to other DILI controls (p = 0.03) and to DILI controls exposed to MP (p = 0.04).

Conclusion: MP DILI is characterised by hepatocellular injury, short latency and generally rapid recovery. There was no independent HLA haplotype associated with MP DILI.

Keywords: HLA genotype associations; drug induced liver injury; methylprednisolone; multiple sclerosis.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / genetics
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects
  • HLA-DQ alpha-Chains / genetics
  • HLA-DQ beta-Chains / genetics
  • HLA-DRB1 Chains* / genetics
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Methylprednisolone* / administration & dosage
  • Methylprednisolone* / adverse effects
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Retrospective Studies
  • United States

Substances

  • Methylprednisolone
  • HLA-DRB1 Chains
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DQ alpha-Chains
  • HLA-DQA1 antigen
  • Glucocorticoids